We propose to extend and develop our studies of the structural role of cholesterol and its fatty acid esters in membranes and atherosclerotic lesions. The proposed studies fall in three broad areas. 1. Uniformly deuterated cholesterol will be synthesized and used in neutron scattering studies of cholesteryl ester phases, phospholipid-cholesterol mixtures, and biological membranes. The conformation of individual cholesterol ester molecules in cholesteryl ester phases and in phospholipid bilayers will be determined, the planar organization of cholesterol in lipid bilayers and membranes will be explored, and the organization of cholesterol and cholesteryl esters with respect to the profile structure of lipid bilayers will be established. 2. A novel density gradient separation method will be exploited to prepare isolated droplets which are in the smectic or isotropic states at body temperature from homogenized atherosclerotic lesions. Compositional studies will establish the molecular features responsible for the state of these droplets. The distribution of droplet states will be used in comparative studies of different lesions, different areas of a given artery specimen, and arteries from different individuals. Correlation with risk factors will be sought to explore the significance of droplet states for the atherosclerotic process. 3. The compositional mapping techniques which we have developed will be used to extend our base of information concerning fatty streak lesions. Additionally, more complex lesions will be studied. Again, the correlation with risk factors will be explored.